Background: Schizophrenia affects around 1% of the global population. Functional connectivity extracted from resting-state functional magnetic resonance imaging (rs-fMRI) has previously been used to study schizophrenia and has great potential to provide novel insights into the disorder. Some studies have shown abnormal functional connectivity in the default mode network (DMN) of individuals with schizophrenia, and more recent studies have shown abnormal dynamic functional connectivity (dFC) in individuals with schizophrenia. However, DMN dFC and the link between abnormal DMN dFC and symptom severity have not been well-characterized. Method: Resting-state fMRI data from subjects with schizophrenia (SZ) and healthy controls (HC) across two datasets were analyzed independently. We captured seven maximally independent subnodes in the DMN by applying group independent component analysis and estimated dFC between subnode time courses using a sliding window approach. A clustering method separated the dFCs into five reoccurring brain states. A feature selection method modeled the difference between SZs and HCs using the state-specific FC features. Finally, we used the transition probability of a hidden Markov model to characterize the link between symptom severity and dFC in SZ subjects. Results: We found decreases in the connectivity of the anterior cingulate cortex (ACC) and increases in the connectivity between the precuneus (PCu) and the posterior cingulate cortex (PCC) (i.e., PCu/PCC) of SZ subjects. In SZ, the transition probability from a state with weaker PCu/PCC and stronger ACC connectivity to a state with stronger PCu/PCC and weaker ACC connectivity increased with symptom severity. Conclusions: To our knowledge, this was the first study to investigate DMN dFC and its link to schizophrenia symptom severity. We identified reproducible neural states in a data-driven manner and demonstrated that the strength of connectivity within those states differed between SZs and HCs. Additionally, we identified a relationship between SZ symptom severity and the dynamics of DMN functional connectivity. We validated our results across two datasets. These results support the potential of dFC for use as a biomarker of schizophrenia and shed new light upon the relationship between schizophrenia and DMN dynamics.
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Transient states of network connectivity are atypical in autism: A dynamic functional connectivity study
There is ample evidence of atypical functional connectivity (FC) in autism spectrum disorders (ASDs). However, transient relationships between neural networks cannot be captured by conventional static FC analyses. Dynamic FC (dFC) approaches have been used to identify repeating, transient connectivity patterns (“states”), revealing spatiotemporal network properties not observable in static FC. Recent studies have found atypical dFC in ASDs, but questions remain about the nature of group differences in transient connectivity, and the degree to which states persist or change over time. This study aimed to: (a) describe and relate static and dynamic FC in typical development and ASDs, (b) describe group differences in transient states and compare them with static FC patterns, and (c) examine temporal stability and flexibility between identified states. Resting‐state functional magnetic resonance imaging (fMRI) data were collected from 62 ASD and 57 typically developing (TD) children and adolescents. Whole‐brain, data‐driven regions of interest were derived from group independent component analysis. Sliding window analysis and k‐means clustering were used to explore dFC and identify transient states. Across all regions, static overconnnectivity and increased variability over time in ASDs predominated. Furthermore, significant patterns of group differences emerged in two transient states that were not observed in the static FC matrix, with group differences in one state primarily involving sensory and motor networks, and in the other involving higher‐order cognition networks. Default mode network segregation was significantly reduced in ASDs in both states. Results highlight that dynamic approaches may reveal more nuanced transient patterns of atypical FC in ASDs.
more » « less- NSF-PAR ID:
- 10460534
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Human Brain Mapping
- Volume:
- 40
- Issue:
- 8
- ISSN:
- 1065-9471
- Page Range / eLocation ID:
- p. 2377-2389
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Functional magnetic resonance imaging (fMRI) studies have shown altered brain dynamic functional connectivity (DFC) in mental disorders. Here, we aim to explore DFC across a spectrum of symptomatically‐related disorders including bipolar disorder with psychosis (BPP), schizoaffective disorder (SAD), and schizophrenia (SZ). We introduce a group information guided independent component analysis procedure to estimate both group‐level and subject‐specific connectivity states from DFC. Using resting‐state fMRI data of 238 healthy controls (HCs), 140 BPP, 132 SAD, and 113 SZ patients, we identified measures differentiating groups from the whole‐brain DFC and traditional static functional connectivity (SFC), separately. Results show that DFC provided more informative measures than SFC. Diagnosis‐related connectivity states were evident using DFC analysis. For the dominant state consistent across groups, we found 22 instances of hypoconnectivity (with decreasing trends from HC to BPP to SAD to SZ) mainly involving post‐central, frontal, and cerebellar cortices as well as 34 examples of hyperconnectivity (with increasing trends HC through SZ) primarily involving thalamus and temporal cortices. Hypoconnectivities/hyperconnectivities also showed negative/positive correlations, respectively, with clinical symptom scores. Specifically, hypoconnectivities linking postcentral and frontal gyri were significantly negatively correlated with the PANSS positive/negative scores. For frontal connectivities, BPP resembled HC while SAD and SZ were more similar. Three connectivities involving the left cerebellar crus differentiated SZ from other groups and one connection linking frontal and fusiform cortices showed a SAD‐unique change. In summary, our method is promising for assessing DFC and may yield imaging biomarkers for quantifying the dimension of psychosis.
Hum Brain Mapp 38:2683–2708, 2017 . ©2017 Wiley Periodicals, Inc. -
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Abstract Dynamic functional network connectivity (dFNC) is an expansion of traditional, static FNC that measures connectivity variation among brain networks throughout scan duration. We used a large resting‐state fMRI (rs‐fMRI) sample from the PREDICT‐HD study (
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